Co-occurring substance abuse disorders (SUDs) and mental illness is a major problem in contemporary mental health. Despite advances in understanding the neuropathophysiology of various forms of mental illness or addictions as ideal, non-overlapping entities, the interaction between these disease processes is poorly understood. This Mentored Clinical Scientist Development Award (K08) seeks support for the career development of a psychiatrist/researcher as a translational neuroscientist focused on understanding the neural mechanisms commonly involved in addictions and psychiatric disorders. This award will further a research program characterizing combined animal models of psychiatric illness and addictions while supporting training needed to apply relevant neurobiological assays to dual diagnosis animal models. This research hypothesizes that neural systems abnormalities that cause psychiatric syndromes also cause increased vulnerability to the neurobehavioral process of addiction, and ultimately, a greater frequency of SUDs in the mentally ill. Building on previous work demonstrating an accelerated addiction pattern to cocaine in the neonatal ventral hippocampal lesion (NVHL) rat model of schizophrenia, this research will explore the neurobiological correlates of a sensitizing regimen of daily cocaine injections, the NVHL, and their combination, vs. sham-saline controls to uncover neural systems interactions between these addiction and psychiatric disease models. Specific Aim 1 will utilize immunohistochemistry to examine patterns of cocaine-induced immediate-early gene (c-Fos) expression to identify group differences in neuronal activation in forebrain circuits commonly implicated in addictions and mental illness. Specific Aim 2 will utilize microdialysis to examine group differences in cocaine-induced dopamine and serotonin efflux in the NAc. Specific Aim 3 will utilize microarray technology to examine group differences in patterns of gene expression in the Nucleus Accumbens (NAc), Caudate Putamen (CaPu) and medial Prefrontal Codex (mPfC).